Atrophy, inducible satellite cell activation, and possible denervation of supraspinatus muscle in injured human rotator- cuff muscle
Atrophy, inducible satellite cell activation, and possible denervation of supraspinatus muscle in injured human rotator- cuff muscle
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DOI：
10.1152/ajpcell.00143.2015
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发表时间：
2015-09-15
影响因子：
5.5
通讯作者：
Anderson, Judy E.
中科院分区：
文献类型：
--
作者：
Gigliotti, Deanna;Leiter, Jeff R. S.;Anderson, Judy E.
肩部肩袖损伤（RCI）手术修复后的不良预后和慢性疼痛的高频率促使本研究探索使用一氧化氮（NO）为基础的治疗来扩大肌肉再生的潜力。术前磁共振成像（MRI）后，在RCI修复手术中收集冈上肌和同侧三角肌（作为对照）的活检。肌纤维直径、alphabungarotoxin染色观察到的神经肌肉连接模式以及Western blots中乙酰胆碱受体的γ:epsilon亚基比，与实验相结合，以确定肌肉卫星细胞对no供体药物硝酸异山酸酯（ISDN）激活（通过摄取溴脱氧尿苷，BrdU）的体外反应性。与冈上肌萎缩的MRI表现（占位率降低，切线征）一致，冈上肌纤维直径小于三角肌。培养40小时后，ISDN诱导冈上肌中BrdU +（活化）Pax7 +卫星细胞的比例比基线显著增加（高达1.8倍），而三角肌中没有。去神经支配指数的新应用显示冈上肌比三角肌具有更高的gamma:epsilon亚单位比值（P = 0.13）；该比例与占据率（P < 0.05）和神经肌肉连接处簇的比例（P = 0.05）成反比。结果提示RCI中可能存在冈上肌去神经支配，并提示no供体治疗有可能促进RCI后萎缩的冈上肌的生长并改善功能预后。
The high frequency of poor outcome and chronic pain after surgical repair of shoulder rotator-cuff injury (RCI) prompted this study to explore the potential to amplify muscle regeneration using nitric oxide (NO)based treatment. After preoperative magnetic resonance imaging (MRI), biopsies of supraspinatus and ipsilateral deltoid (as a control) were collected during reparative surgery for RCI. Muscle fiber diameter, the pattern of neuromuscular junctions observed with alphabungarotoxin staining, and the gamma:epsilon subunit ratio of acetylcholine receptors in Western blots were examined in tandem with experiments to determine the in vitro responsiveness of muscle satellite cells to activation (indicated by uptake of bromodeoxyuridine, BrdU) by the NO-donor drug, isosorbide dinitrate (ISDN). Consistent with MRI findings of supraspinatus atrophy (reduced occupation ratio and tangent sign), fiber diameter was lower in supraspinatus than in deltoid. ISDN induced a significant increase over baseline (up to 1.8-fold), in the proportion of BrdU + (activated) Pax7 + satellite cells in supraspinatus, but not in deltoid, after 40 h in culture. The novel application of denervation indices revealed a trend for supraspinatus muscle to have a higher gamma:epsilon subunit ratio than deltoid (P = 0.13); this ratio inversely with both occupancy ratio (P < 0.05) and the proportion of clusters at neuromuscular junctions (P = 0.05). Results implicate possible supraspinatus denervation in RCI and suggest NO-donor treatment has potential to promote growth in atrophic supraspinatus muscle after RCI and improve functional outcome.